Endometrial cancer refers to the malignancies of endometrium of the uterus. It is the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. It represents the third most common cause of gynecologic cancer death, behind ovarian and cervical cancer (Siegel, Ca Cancer J Clin. 63:11-30 (2013)). Endometrioid adenocarcinoma often develops in the setting of endometrial hyperplasia, and presents with vaginal bleeding. The most common therapeutic approach of endometrial cancer is a total abdominal hysterectomy with bilateral salpingo-oophorectomy.
When discovered in its early stages, endometrial cancer is highly curable (Engelsen, APMIS 117: 693-707 (2009)). There are presently several methods of clinical evaluation for the presence of endometrial cancer, including Pap smear. Notably, Pap smear is ineffective in detecting endometrial cancer, while it is useful in screening for cervical cancer. Office endometrial biopsy still remains the traditional diagnostic method, in which both endometrial and endocervical materials are often sampled. In the event that endometrial biopsy does not yield sufficient diagnostic material, a dilation and curettage (D&C) is necessary for diagnosing the cancer. Hysteroscopy permits the direct visualization of the uterine cavity and can be used to detect the presence of lesions or tumors. However, such procedure is not practical because it requires strict sterile environments and physician's competent skill, as well as the high associated costs.
Transvaginal ultrasound is a non-invasive method that is used to evaluate the endometrial thickness in women with postmenopausal bleeding and is increasingly being used to evaluate for endometrial cancer. However, the method is often not sensitive to detect early endometrial cancer. Studies suggest measurement of serum p53 antibody may be used to identify high-risk endometrial cancer.
There are currently no other specific biomarkers that exist for endometrial cancer as diagnosis is usually dependent on histology. Several potential biomarkers have been correlated to endometrial cancer in studies, but often these results are inconsistent (Engelsen, APMIS 117: 693-707 (2009)), thus making it difficult to develop a therapy.
Brest cancer may also undergo the epithelial to mesenchymal transition as in endometrial cancer. In the USA, 180,000 women are diagnosed annually with new cases of breast cancer and it is the second leading cause of cancer-related death in women in the US (Polyak, et al., Biochim Biophys Acta. 2001 Nov. 30; 1552(1):1-13).
Breast cancers are generally treated by targeting the estrogen, progesterone or human epidermal growth factor receptor type 2 (HER2) receptors. Clinical trials on humans using anti-cancer drugs and anti-HER2 antibodies have been conducted and achieved improved clinical response and overall survival (Molin, M A, et al., Cancer Res 61: 4744-4749 (2001)). But in the case of triple negative breast cancer (TNBC), such targeted treatment is ineffective because TNBC lacks estrogen receptors, progesterone receptors, and human epidermal growth factor receptor type 2 (HER2/neu). While TNBC does respond to chemotherapeutics, TNBC becomes aggressive. Treatment with chemotherapy unfortunately has high recurrence and poor clinical outcome.
Accordingly, there is a continuing need in identifying potential biomarker for endometrial cancer and breast cancer in humans and novel compounds that inhibit epithelial to mesenchymal transition and thus inhibit endometrial and breast cancer development and growth.